POS1237 SARS-CoV-2 mRNA VACCINE IMMUNOGENICITY IN CHRONIC INFLAMMATORY ARTHRITIS ON DMARD THERAPY
Authors: N. Darwish, S. Jhaveri, U. Yoganathan, H. Bakillah, K. Chun, T. Wasser, J. Freeman
Journal: Annals of the Rheumatic Diseases (2022)

Background Patients with chronic inflammatory arthritis (CIA) are at increased risk for the development and mortality from COVID-19 1 . Vaccinations are integral to the management of these conditions. Disease-modifying antirheumatic drugs (DMARDs) used to treat CIA have the potential to blunt the immune response and efficacy of vaccinations 2 . There is little data on the effect of DMARDS used for CIA on the response to novel mRNA vaccines, limiting guidelines to direct therapy. Objectives Assess the antibody response (ABR) to the SARS-CoV-2 mRNA vaccines in patients with CIA on treatment with either methotrexate (MTX), tumor necrosis factor inhibitors (TNFi), or both with healthy controls. Determine the effect of interrupting therapy after vaccination in patients with CIA on the ABR to the vaccine. Methods 63 patients with rheumatoid or psoriatic arthritis on MTX, TNFi or both were recruited from a community-based rheumatology practice. All subjects received two doses of a mRNA COVID vaccine. Use of hydroxychloroquine (HCQ), NSAID’s, and prednisone (Pred) ≤10mg daily were allowed. Those with prior COVID infection were excluded, as determined by SARS-CoV-2 nucleocapsid assay. 26 healthy age-matched controls were obtained from banked blood from Labcorp. IRB approval was obtained, and patients were consented to participate in the study. SARS anti-receptor binding domain IgG antibodies were measured by electro chemiluminescent immunoassay 90-120 days post initial vaccine dose. Patients were divided into 3 groups based on therapy: 1. MTX monotherapy 2. TNFi with eternacept (ETN) or adalimumab (ADA) 3. A combination of MTX with either ETN or ADA Each of the groups were subdivided into two categories: 1. Continued treatment uninterrupted at the time of each of the two vaccines. 2. Held treatment for two weeks after each vaccine. Statistical significance (p&lt;.005) determined using one way ANOVA with Scheffe procedure and Student’s T-test. Results The 63 patients with CIA had a significantly lower ABR to vaccine compared with healthy controls (p=0.001). Further analysis was limited by sample size: The MTX held group had a higher ABR than the MTX continued group (mean IgG=35.5 vs 21.74; p=0.14), demonstrating a trend toward increased immunogenicity. There was a similar ABR to vaccine between those on TNFi who held vs continued therapy (mean IgG 20.83 vs 28.65; p=0.525). Combination MTX +TNFi held vs continued groups demonstrated a trend toward increased immunogenicity when holding therapy post vaccine (mean IgG 42.4 vs 22.7; p=0.44). All treatment groups were comparable in Pred, HCQ, NSAID use, age, Rapid 3 score, and time between vaccination and blood draw for antibody levels (VI). Table 1. Antibody response to Vaccination Variable MTX TNF MTX + TNFi Controls p value Test M SD M SD M SD M SD IgG 28.95 30.01 23.96 14.77 35.27 38.81 66.31 38.06 0.001 ANOVA Drug Variable Held Continued p value n M SD n M SD MTX Age 22 67.95 7.33 20 71.3 11.07 0.251 T-test IgG 22 35.5 29.92 20 21.74 29.13 0.14 VI 22 97.27 13.71 20 98.15 10.19 0.817 TNFi Age 6 64.5 10.19 4 70.25 13.77 0.467 IgG 6 20.83 10.07 4 28.65 20.9 0.525 VI 6 98.67 22.24 4 93.75 12.29 0.701 MTX + TNFi Age 7 63.86 6.36 4 62.75 11.53 0.839 IgG 7 42.43 45.11 4 22.75 24.92 0.448 VI 7 100 19.09 4 97.75 22.59 0.864 Variable CIA Controls p value n M SD n M SD Age 63 63.05 9.61 26 52.31 8.84 0.001 T-test VI 63 97.79 14.31 26 88.65 5.43 0.002 M: Mean; VI: Vaccine Interval in days Conclusion The ABR in patients with CIA to the mRNA vaccine appeared to be blunted by ongoing therapy with MTX. This effect was attenuated by holding MTX post-vaccine. There was no significant difference in the ABR to vaccine in patients on TNFi who held vs continued these agents after vaccine, due to small sample size. Patients with CIA on DMARD therapy had a significantly lower ABR to the vaccine compared to healthy controls. Our findings need further validation in a larger cohort. Clinicians may consider holding MTX for two weeks post vaccination to optimize the immune response to the vaccine. References [1]Sepriano A, et al. Ann Rheum Dis. 2020;79(6):760-770 [2]Hua C, et al. Arthritis Care Res 2014;66(7):1016-1026 Acknowledgements We would like to thank Jamie Reidy and Judy Wolf for their efforts in the Arnot laboratory, Dr. Manav Bandlamudi and Dr. Frank Edwards for their research support. Disclosure of Interests None declared